Clinical observations of alpha1-antitrypsin deficient patients indicate a relationship between hepatic inclusions and the deficiency of serum antitrypsins. The purpose of this research study is to develop animal models by which the relationship of hepatic glycoprotein metabolism and serum protease inhibitor (SPI) deficiency may be explored. We have produced a reversible deficiency state of serum antiproteases by administration of D-Gal in doses of 200-600 mg/kg daily. Depression of SPI below 50% of controls may cause death from hemorrhage or hepatic insufficiency. Future studies will attempt to induce controlled depression of SPI levels at or near 10% of controls, by modifying the dosage schedule, utilizing other animal species and other metabolic antagonists such as, 2-deoxyglucose alone in combination with 6-agauridine. The hepatic inclusions produced by D-Gal administration have been isolated by density gradient centrifugation. Immunochemical methods have been applied to identify the serum protein content of the isolated inclusions. Further immunochemical characterization of the hepatic inclusions in the D-Gal or similar models will be studied and compared to the serum proteins. Additional studies will be performed in which the concentrations and amounts of elastase introduced into the lung will be varied along with production of more severe depressions of circulating antiproteases. Elastase induced injury will also be attempted by its introduction intraveneously. Mouse species of different genetic strains will be evaluated in order to develop an optimal animal model. BIBLIOGRAPHIC REFERENCES: Kleinerman, J., and Rynbrandt, D. J.: Lung proteolytic activity and serum protease inhibition after NO2 exposure. Arch. Environ. Health. 31: 37, 1976. Liotta, L. A., Kleinerman, J., and Saidel, G.: The inhibition of pulmonary metastases by BCG. Accepted for program. Amer. Assoc. Path & Bact., March 1976 (Abstract).